2.4 Excretion
Excretion is the removal of drugs and metabolites from the body. The kidneys are the primary route, with biliary excretion also important for large/polar compounds.
Renal Excretion
Glomerular Filtration
Free drug filtered (not protein-bound). GFR ~120 mL/min. MW <20,000 Da.
Active Tubular Secretion
OAT, OCT transporters in proximal tubule. Can excrete protein-bound drugs.
Tubular Reabsorption
Passive diffusion of unionized drug. pH-dependent (urine alkalinization/acidification).
Clearance
\( CL = \frac{\text{Rate of elimination}}{\text{Plasma concentration}} = \frac{Dose}{AUC} \)
Renal Clearance
CLrenal = (fu × GFR) + CLsecretion - CLreabsorption
Hepatic Clearance
CLhepatic = Q × E (blood flow × extraction ratio)
Half-Life
\( t_{1/2} = \frac{0.693 \times V_d}{CL} \)
Time for plasma concentration to decrease by 50%. Used to determine dosing interval.
Clinical note: ~97% drug eliminated after 5 half-lives. Steady state reached after 4-5 half-lives of continuous dosing.
Other Excretion Routes
Biliary Excretion
Large MW (>500), polar conjugates. Enterohepatic circulation possible.
Pulmonary
Volatile anesthetics, alcohol (breathalyzer).
Sweat/Saliva
Minor route. Some drugs detectable for monitoring.
Breast Milk
Lipophilic drugs pass. Infant exposure consideration.